Gene Therapy for Hunter Syndrome

Overseen By Patient Advocacy

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: REGENXBIO Inc.

Must not be taking: Methylprednisolone, Tacrolimus, Sirolimus, Prednisone

Disqualifiers: Renal insufficiency, Uncontrolled hypertension, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a gene therapy called RGX-121, designed to treat Hunter Syndrome by delivering a working copy of a specific gene to the brain. Researchers seek to determine the safety, effectiveness, and patient tolerance of this treatment. Boys diagnosed with Hunter Syndrome who show signs of a specific type of brain involvement might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial requires participants to stop taking certain medications, like idursulfase (ELAPRASE) via IT administration or a blood brain barrier-crossing ERT, at least 3 months before starting the trial and for the duration of the study. If you are on these therapies, you will need to discontinue them.

Is there any evidence suggesting that RGX-121 is likely to be safe for humans?

Research has shown that RGX-121, a gene therapy for Hunter Syndrome, has promising safety results. In earlier studies, about 12 months after treatment, RGX-121 demonstrated positive outcomes without major safety issues. This therapy provides a working copy of a gene missing in people with Hunter Syndrome.

Reports indicate that RGX-121 is generally well-tolerated. No serious side effects have been directly linked to the treatment in the studies so far. While minor side effects can occur, current research considers the therapy safe.

For those considering joining a trial, it is reassuring that RGX-121 has been tested in other studies with good safety results. However, always discuss any concerns with the trial team and your doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Hunter Syndrome?

Researchers are excited about RGX-121-3102 for Hunter Syndrome because it uses a novel gene therapy approach. Unlike current treatments, which primarily aim to manage symptoms through enzyme replacement therapy, RGX-121-3102 delivers a gene directly into the brain using an AAV9 vector. This method targets the root cause of the disorder by introducing a functional copy of the IDS gene, potentially leading to long-term benefits and improved cognitive outcomes. This innovative approach offers hope for more effective and sustained treatment outcomes for those affected by Hunter Syndrome.

What evidence suggests that RGX-121 might be an effective treatment for Hunter Syndrome?

Research has shown that RGX-121 gene therapy, which participants in this trial will receive, could help treat Hunter Syndrome. In earlier studies, a single dose of RGX-121 improved patients' conditions by providing the brain with a working copy of a needed gene. This treatment led to significant improvements in brain function, which current enzyme treatments do not achieve. Additionally, data from 12 months demonstrated positive effects on brain function for those who received RGX-121. These results suggest that RGX-121 might help prevent the decline in brain function seen in severe cases of Hunter Syndrome. ^{1 2 3 4 6}

Who Is on the Research Team?

Alexander Schramm

Principal Investigator

St. Peters University Hospital

Are You a Good Fit for This Trial?

This trial is for patients with Hunter Syndrome, a genetic disorder that affects the body's ability to break down certain sugars. Participants should have a diagnosis of Mucopolysaccharidosis II (MPS II) and be in stable health otherwise.

Inclusion Criteria

Has a BSID-III Cognitive Composite score at or below -1SD (85) from the normative mean.

I have been diagnosed with neuronopathic MPS II.

The participant's legal guardian(s) is (are) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any study-related procedures being performed.

Exclusion Criteria

I have had a stem cell transplant.

I am willing to stop my current treatment with ELAPRASE or a similar therapy 3 months before starting RGX-121.

Has an absolute neutrophil count (ANC) < 1.0 × 103/µL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time dose of RGX-121 gene therapy to deliver a functional copy of the iduronate-2-sulfatase gene to the CNS

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including assessments of CSF and plasma biomarkers, neurodevelopmental function, and auditory capacity

5 years

Multiple visits over 5 years

Long-term Follow-up

Long-term monitoring of safety and efficacy, including changes in biomarkers and neurodevelopmental parameters

5 years

What Are the Treatments Tested in This Trial?

Interventions

• RGX-121-3102

Trial Overview The trial is testing RGX-121-3102, a gene therapy designed to deliver a working copy of the IDS gene directly to the central nervous system. The goal is to see if it's safe, effective, and tolerated well by those with MPS II.

How Is the Trial Designed?

Group I: 2.9×1011 GC/g brain mass of RGX 121 Experimental Treatment 1 Intervention

AAV9.CB7.hIDS

Who Is Running the Clinical Trial?

REGENXBIO Inc.

Lead Sponsor

Trials

25

Recruited

3,100+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07236606

RGX-121-3102 Gene Therapy in Participants With MPS II ... This is a Phase III, open-label, confirmatory study investigating the efficacy, safety, and pharmacodynamics of RGX-121 treatment of patients with neuronopathic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10875268/

Comparative dose effectiveness of intravenous and intrathecal ... We conclude that a dose of 1 × 1010 gc normalized metabolic and skeletal outcomes, while neurologic improvement required a dose of 1 × 1011 gc, thereby ...

3. ir.regenxbio.com ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-twelve-month-pivotal-data-phase

Release Details 12-month pivotal data further demonstrate the ability of one-time RGX-121 treatment to improve outcomes for patients with MPS II.

4. neurology.org neurology.org/doi/10.1212/WNL.96.15_supplement.4164

RGX-121 gene therapy for severe Mucopolysaccharidosis ... Severe MPS II results in irreversible neurocognitive decline and behavioral symptoms that are not addressed by intravenously administered enzyme ...

5. experts.umn.edu experts.umn.edu/en/publications/comparative-dose-effectiveness-of-intravenous-and-intrathecal-aav

Comparative dose effectiveness of intravenous and ... Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice. Miles C. Smith ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1878747925002193

Rescue of neurologic disease in mucopolysaccharidosis ... Adeno-associated virus (AAV)-mediated gene therapy has emerged as a promising strategy for MPS II. Clinical trials of RGX-121 (AAV9.CB7.hIDS), ...